Optical resolution agent and process for the preparation of the same

ABSTRACT

An optical resolution agent which is prepared by polymerizing a polysaccharide derivative having vinyl groups introduced into the hydroxyl groups thereof through an ester or urethane linkage on the surface of a porous support or by copolymerizing such a polysaccharide derivative having vinyl groups introduced thereinto with a porous support having vinyl groups introduced thereinto and which enables an efficient optical resolution of a racemic modification by chromatography.

TECHNICAL FIELD

The present invention relates to an optical resolution agent and aprocess for the preparation of the same. Particularly, it relates to anoptical resolution agent preferable as a packing for high-performanceliquid chromatography which is prepared by polymerizing a vinylderivative of a polysaccharide such as cellulose and the like on thesurface of a porous support (particle) and a process for the preparationof the same.

BACKGROUND ART

It has been well known that a polysaccharide such as starch, dextran,cellulose, cellulose derivatives and the like exhibit respective uniqueoptical resolving powers. Particularly, it has already been found thatcellulose derivatives prepared by esterifying the hydroxyl groups ofcellulose, i.e., chemically modified celluloses such as cellulosetriacetate and the like are superior to cellulose itself in respect ofoptical resolving power.

When a substance as described above having an optical resolving power isas such used as a packing for liquid chromatography in the directresolution of an optical isomer mixture by liquid chromatography, theservice conditions of the column are disadvantageously narrowed, becausethe packing composed of the substance is poor in pressure resistance andis swollen or shrunken with the solvent used. In order to overcome thisadvantage, it is generally thought a means that the substance issupported on a support free from such problematic properties and theproduct is used.

Under these circumstances, the impregnation-adsorption process, i.e., aphysical process which comprises dipping a support in a solution of theabove substance, recovering the support and drying it occurs to us asone of the easiest processes for supporting the substance. However, thedisadvantage still remains that only few kinds of solvents are usablewhen a measurement and an operation is conducted with a chromatograph,because it is undesirable to use a solvent which dissolves thesubstance. This disadvantage is generally more significant when achemically modified polysaccharide is used. That is, the developer to beused in the chromatography using the modified polysaccharide must be onewhich does not dissolve the modified polysaccharide, because of the highsolubility of the modified polysaccharide in an organic solvent, whichrestricts the selection of the resolution conditions severely. Further,there is also a limitation in the selection of the solvent to be usedfor dissolving a sample, because a chemically modified polysaccharidehas a problem that the number of theoretical plates thereof isremarkably lowered even by the injection of only several microliters ofa good solvent therefor.

Although the chemical bonding of a polysaccharide derivative asdescribed above to a support may be thought to be effective inovercoming the above disadvantage of the physical process, no specificmeans have been proposed as yet on how to chemically bond thepolysaccharide derivative to a support while maintaining the excellentoptical resolving power of the polysaccharide derivative. For example,although Japanese Patent Publication-A No. 82858/1985 discloses that achemical process as well as a physical one can be employed in supportinga polysaccharide derivative on a support, no specific description on thechemical process is found in this patent document.

DISCLOSURE OF THE PRESENT INVENTION

The present invention has been made under these circumstances and anobject thereof is to provide a support for the optical resolution whichuses a chemically modified polysaccharide (polysaccharide derivative)and which places little limitation on the developer to be used in liquidchromatography or the solvent to be used for dissolving a sample.

Namely, as the result of the extensively studies, the present inventorshave found that a polymeric optically active support which is completelyinsoluble in a solvent exhibiting a high dissolving power for thechemically modified polysaccharide of the prior art, e.g., ethylacetate, tetrahydrofuran, methylene chloride, chloroform, acetone, etc.,can be obtained by, for the purpose of insolubilizing a chemicallymodified polysaccharide, chemically modifying the hydroxyl groups of apolysaccharide with a specified modifying agent having a vinyl group toform a polysaccharide derivative having vinyl groups introducedthereinto through an ester or urethane linkage and polymerizing thepolysaccharide derivative on the surface of a porous support. Thepresent invention has been accomplished on the basis of this finding.

Accordingly, the characteristic of the optical resolution agent of thepresent invention is that the agent is one prepared by polymerizing apolysaccharide derivative having vinyl groups introduced into thehydroxyl groups thereof through an ester or urethane linkage on thesurface of a porous support, particularly advantageously one prepared bycopolymerizing such a polysaccharide derivative with a porous supporthaving vinyl groups introduced thereinto.

Further, the present invention also include that, for obtaining theoptical resolution agent described above, a polysaccharide derivativehaving vinyl groups introduced into the hydroxyl groups thereof throughan ester or urethane linkage is adhered or adsorbed on the surface of aporous support and then polymerization of the polysaccharide derivativeis conducted, or that polymerization of such a polysaccharide derivativeis conducted with at least part of the polysaccharide derivative beingcopolymerized with the vinyl groups of a porous support.

Although the polysaccharide into which vinyl groups are introducedaccording to the present invention is representatively cellulose, otherpolysaccharide such as dextran, amylose, curdlan, pullulan and the likemay be suitably used. Further, it is desired that the cellulose to beused in the present invention have a low molecular weight correspondingto, for example, a number-average degree of polymerization of 100 orbelow for spreading a uniform cellulose derivative on a porous supportuniformly, because the viscosity of a solution of a chemically modifiedcellulose prepared by the chemical modification of a cellulose increasesas the molecular weight of the chemically modified cellulose increases,so that it becomes difficult more by more to cause the chemicallymodified cellulose to be adhered or adsorbed uniformly on the surface ofa porous support.

The introduction of vinyl groups into such a polysaccharide by chemicalmodification must be conducted by introducing vinyl groups (specificallyvinyl-containing organic groups) into the hydroxyl groups of apolysaccharide through an ester or urethane linkage in order to maintainthe excellent optical resolving power of the polysaccharide.

The modifying agent to be used in the chemical modification of such apolysaccharide may be suitably selected from among known vinyliccompounds which react with the hydroxyl group of a polysaccharide toform an ester or urethane linkage. Examples of the modifying agentinclude unsaturated acid halides such as acryloyl chloride, methacryloylchloride, vinylbenzoyl chloride and the like; and unsaturatedisocyanates such as vinylphenyl isocyanate and the like. Further,compounds having more than one vinyl group in the molecule as well asthe above compounds having one vinyl group in the molecule may be usedat need. Furthermore, in a case wherein a vinylic compound having astructure comprising a benzene ring and a vinyl group bonded to the ringis used, no significant trouble occurs with respect to the bondingposition of the vinyl group even when the vinyl group is bonded to thering at any of the ortho, meta and para positions, so far as thecompound is polymerizable.

With respect to the introduction number of the vinyl group per aconstituent unit of a polysaccharide when the chemically modification ofa polysaccharide is conducted with a vinylic compound, all of thehydroxyl groups present in the constituent unit of a polysaccharide(e.g., three hydroxyl groups in the case of cellulose) need not becompletely modified with a vinylic compound as described above, but apolysaccharide may be chemically modified with a vinylic compound tosuch an extent that the chemically modified polysaccharide can bedissolved in a good solvent such as methylene chloride and the like, bywhich the objective polymerization of the modified polysaccharide on thesurface of a support can be attained.

Meanwhile, the porous support to be applied such a polysaccharide havingvinyl groups introduced thereinto according to the present inventionincludes known ones such as inorganic porous supports, e.g., silica,alumina, magnesia, titanium oxide, glass, silicates, kaolin, etc., andorganic porous supports, e.g., polystyrene, polyamide, polyacrylate,etc., among which porous particles such as silica (silica gel) and glass(porous glass) are preferably used.

In the present invention, these porous supports may be each used as suchor may be modified by the introduction of vinyl groups prior to the usefor supporting the polysaccharide having vinyl groups introducedthereinto more effectively. In the latter case, copolymerization betweenthe polysaccharide having vinyl groups introduced thereinto and theporous support having vinyl groups introduced thereinto is conducted tothereby provide an optical resolution agent insolubilized in organicsolvents, more effectively.

Various known processes can be employed in the introduction of vinylgroups into a porous support. The introduction can be conducted by themethod same as one for bonding vinyl groups to a polysacchalidedescribed above. Namely, a given porous support, preferably a chemicallymodifiable support such as silica gel, porous glass, etc., is reactedwith a vinylic compound which may have more than one vinyl group or mayhave a vinyl group at any position to such an extent as to exert littleadverse effect on the function of the copolymerizability to bond thevinylic compound to the porous support. Therefore, objective vinylgroups are introduced into the porous support.

Specific processes for introducing vinyl groups to a porous support willnow be listed next, wherein silica gel is used as the porous support.

    ______________________________________                                        I.Process for reacting a silylating agent having a                            vinyl group with the hydroxyl group of silica gel                              ##STR1##                                                                     styrylethylated silica gel                                                    II.Process for introducing a functional group                                 reactive with a compound having a vinyl group to                              the surface of silica gel and bonding vinyl groups                            to the resulting surface                                                       ##STR2##                                                                     aminopropylated silica gel                                                    a)aminopropylated silica gel + acryloyl                                        ##STR3##                                                                     b)aminopropylated silica gel + methacryloyl                                    ##STR4##                                                                     c)aminopropylated silica gel + vinylphenyl                                     ##STR5##                                                                     (2)silica gel + O-trimethylsilylpropyldimethylchloro-                          ##STR6##                                                                     d)hydroxypropylated silica gel + acryloyl                                      ##STR7##                                                                     e)hydroxypropylated silica gel + vinylphenyl                                   ##STR8##                                                                     (3)silica gel + glycidoxypropyltrimethoxy-                                     ##STR9##                                                                     f)glyceroylpropylated silica gel + acryloyl                                    ##STR10##                                                                    III.Process for bonding a silylating agent with a compound                    having a vinyl group and then bonding the reaction                            product to silica gel                                                         a)aminopropyltriethoxysilane + acryloyl                                        ##STR11##                                                                     ##STR12##                                                                    b)aminopropyltriethoxysilane + methacryloyl                                    ##STR13##                                                                     ##STR14##                                                                    c)aminopropyltriethoxysilane + vinylphenyl                                     ##STR15##                                                                     ##STR16##                                                                    ______________________________________                                    

Since the above-described porous support is used in the presentinvention, the processes for the preparation of an optical resolutionagent which is described above and which is prepared by polymerizing apolysaccharide having vinyl groups introduced thereinto are classifiedroughly into two groups, i.e., a group consisting of processes using asupport having vinyl groups bonded thereto as the porous support and agroup consisting of processes using a support having no vinyl group. Asupport having vinyl groups introduced thereinto and an unmodifiedsupport are different from each other in respect of surface polarity, sothat they may be different from each other in the amount of adsorptionof the vinylated polysaccharide and may release the polysaccharideduring the polymerization to different extents in these preparationprocesses, especially when a polysaccharide having vinyl groupsintroduced thereinto is adsorbed to each of the supports. However, sameprocedure can be applied to both of the supports with respect to theadsorption process and polymerization conditions. For example, theoptical resolution agent according to the present invention can beprepared by applying a solution of the polysaccharide having vinylgroups introduced thereinto to the surface of a support to cause thepolysaccharide to be adhered or adsorbed on the surface and polymerizingthe polysaccharide by a polymerization method such as radical, ionic orplasma polymerization.

When an unmodified porous support is used, the polysaccharide derivativemay be eluted when the degree of polymerization of the polymer is low,though the object of preventing the dissolution of the polysaccharidederivative even in a good solvent such as methylene chloride can beattained by enhancing the degree of polymerization of the polysaccharidederivative to such an extent that the polymer cannot be dissolved in thegood solvent. On the other hand, when a support having vinyl groupsintroduced thereinto is used, the polysaccharide derivative is bonded tothe support, which prevents the elution of a polymer of thepolysaccharide derivative, even if the polymer cannot acquire such ahigh degree of polymerization as to inhibit dissolution thereof even ina good solvent.

Further it is possible to employ a process for further causing thepolysaccharide having vinyl groups bonded thereto to be adsorbed to theoptical resolution agent prepared by the above polymerization toincrease the amount of the polysaccharide derivative introduced andpolymerizing the polysaccharide derivative to further enhance the degreeof polymerization, because it is inconceivable that all of the vinylgroups present in both the polysaccharide derivative and the support arecompletely polymerized and disappear by only one run of polymerization.In such a process of conducting two or more runs of polymerization, ameans, which comprises using a compound having more than one vinylgroup, such as divinylbenzene, ethylenediamine dimethacrylate, ethyleneglycol diacrylate and the like, as a crosslinking agent in addition tothe polysaccharide derivative having vinyl groups bonded thereto toaccelerate the crosslinking reaction and thereby the solubility of thepolysaccharide derivative polymer in a good solvent being able to befurther lowered, can also be employed.

As the polymerization condition for preparing the polymeric opticalresolution agent according to the present invention, general conditionsused for suspension polymerization can be applied. When water is used asthe medium for the polymerization, however, the ester groups bonded tothe polysaccharide may be hydrolyzed and the polysaccharide having vinylgroups introduced thereinto adsorbed on a porous support through ahydrogen bond may be released from the surface of the support owing tothe cleavage of the hydrogen bond between the polysaccharide and theporous support caused by the intervention of water. The falling off ofthe functional groups including a vinyl group introduced thepolysacharide brings about a lowering in the optical resolving power,and a lowering in the amount of adsorption of the vinylatedpolysaccharide on the porous surface in the polymerization step isthought to be causative of a lowering in the efficiency of introducingthe polysaccharide derivative into the porous surface. For thesereasons, it is desired for the polymerization of the polysaccharidederivative on the porous surface that a solvent which neither hydrolyzesthe ester or urethane linkage nor lowers the amount of adsorption of thepolysaccharide derivative is selected, compared with a process whichcomprises using water as the medium.

Although the polymerization medium which neither decomposes the ester orurethane linkage nor cleaves the hydrogen bond includes low-polarityorganic solvents, the use of a solvent which has a boiling point of 90°C. or above and is liquid at ordinary temperatures is preferable inconsideration of the fact that the polysaccharide derivative is solublein relatively many solvents and the requirement that the reactiontemperature necessary for radical polymerization must be secured. Forthese reasons, alkyl hydrocarbons are thought to be optimum as themedium to be used in the preparation of the optical resolution agent. Asspecific examples of the alkyl hydrocarbon mediums, a straight-chainhydrocarbon having 7 or more carbon atoms, such as heptane, optane,nonane, decane and the like; a molecular hydrocarbon having 7 or morecarbon atoms, such as isooctane and the like; a cyclic hydrocarbon suchas decalin and the like; and a hydrocarbon mixture such as kerosine andthe like are advantageously used.

The polysaccharide derivative having vinyl groups introduced thereinto,which are adhered or adsorbed on the surface of a porous support, ispolymerized to form a layer of a polymeric product of such apolysaccharide derivative on the surface of the support. Particularly,when a porous support having vinyl groups introduced thereinto is used,copolymerization also occurs between the support and the polysaccharidederivative, so that the polymerization product is insoluble in organicsolvents at all. Thus, an optical resolution agent which isinsolubilized against organic solvents can be obtained advantageously.

Actually, there has been ascertained that when the insobubilizedoptically active support of a polysaccharide polymerization type is usedas a packing for high-performance liquid chromatography, opticalresolution can be attained even under such mobile phase conditions thatthe polysaccharide derivative is dissolved to fail in optical resolutionwhen the optical resolution agent of the prior art prepared only bycausing a chemically modified polysaccharide to be adsorbed to silicagel as the base material is employed, and that the insolubilizedoptically active support of a polysaccharide polymerization type is tobecome a support of a polymerization type, the performance of which isnot lowered and the optical resolving power of which is maintained assuch even after the injection and passing of methylene chloride, whichis a representative good solvent for the polysaccharide derivativebefore polymerization.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1 and 2 are graphs respectively showing changes in the number oftheoretical plates and the relative retention value with an increase inthe amount of methylene chloride injected, which were observed inExample 2.

FIGS. 3(a) and (b) are chromatograms observed in Example 2 withdifferent the compositions of the mobile phases each other.

EXAMPLE

Examples according to the present invention will now be given in orderto illustrate the present invention more specifically, though it isneedless to say that the present invention is not limited by thedescription of the Examples at all. Further, it should be noted that theembodiments described in the Examples and the specific descriptionsmentioned above can be changed, modified or improved by those skilled inthe art in such a range as not to deviate from the gist of the presentinvention.

EXAMPLE 1

16.8 g of a low-molecular weight cellulose (having a degree ofpolymerization of about 36) prepared by hydrolyzing acetylcellulose toreduce the molecular weight thereof and removing the acetyl groupstherefrom was dispersed in 250 ml of pyridine, followed by the additionof 89.0 g of 4-vinylbenzoyl chloride. The obtained mixture was heated to80° C. and reacted under stirring for 10 hours. After the completion ofthe reaction, the reaction mixture was poured into 1000 ml of methanolto precipitate 4-vinylbenzoylated cellulose, which was washed withmethanol under filtering by the means of suction and dried at 50° C. Theresulting product was dissolved in 500 ml of methylene chloride tofilter out insolubles. The filtrate was distilled to remove themethylene chloride. Methanol was added to the residue to precipitate asolid. The FT-IR spectrum of the cellulose derivative had an absorptionpeak assignable to a carbonyl group, by which it was ascertained thatthe hydroxyl groups of the glucose, which was a constitution unit of thecellulose, were derived.

Then, 4 g of silica gel as a porous support was dispersed in a solutionof 1 g of the 4-methylbenzoylated cellulose in 50 ml of methylenechloride. The obtained dispersion was distilled in a vacuum at 30° C. toremove the methylene chloride, thereby causing the cellulose derivate tobe adhered or adsorbed on the surface of the silica gel.

Thereafter, 3 g of the silica gel having 4-vinylated cellulose adsorbedthereto was dispersed in 50 ml of n-heptane, followed by the addition of30 mg of benzoyl peroxide. The obtained mixture was stirred at 80° C.for 4 hours to conduct polymerization, by which a layer of a polymericproduct of 4-vinylbenzoylated cellulose was formed on the surface of thesilica gel. After the completion of the polymerization reaction, theresulting silica gel having the layer of a polymeric product formed waswashed with methylene chloride and dried in a vacuum.

The obtained silica gel having the layer of a polymeric product of4-vinylbenzoylated cellulose formed was examined for solubility. As aresult, it was ascertained that the silica gel of this Example wassuperior to one having acetylcellulose, low-molecular weight celluloseor 4-vinylbenzoylated cellulose adsorbed on the surface thereof inrespect of the insolubility in organic solvents and that the opticalresolving power could be fully retained even after the adsorbedcellulose derivative was polymerized.

EXAMPLE 2

An N-acryloylaminopropylated silica gel as a support having vinyl groupsintroduced thereinto was prepared as follows.

Namely, first, 2 g of vacuum-dried silica gel was dispersed in 100 ml oftoluene, followed by the addition of 2 g of aminopropyltriethoxysilaneas a silylating agent. The obtained mixture was reacted for 5 hourswhile distilling off the ethanol formed by the reaction of thesilylating agent with the silanol together with the toluene. Thus, anaminopropylated silica gel was obtained. After the completion of thereaction, the aminopropylated silica gel was washed with methanol, 80%methanol, methanol and chloroform, successively, and dried in a vacuum.

Then, 2 g of the above aminopropylated silica gel was dispersed in 50 mlof chloroform, followed by the addition of 2 ml of acryloyl chloride.The obtained mixture was maintained at 80° C. for 2 hours to conduct areaction, giving an N-acryloylaminopropyl silica gel. After thecompletion of the reaction, the product was washed with methanol andchloroform, successively, and vacuum dried.

The N-acryloylaminopropylated silica gel thus obtained was used. Forcausing the 4-vinylbenzoylated cellulose prepared in the Example 1 to beadsorbed on the surface of the silica gel, 1 g of the cellulosederivative was dissolved in 50 ml of methylene chloridethe to prepare asolution, the above-described N-acryloylaminopropylated silica gel wasadded to and dispersed in the solution, and the obtained mixture wasdistilled in a vacuum at 30° C. to remove the methylene chloride, thuscausing the cellulose derivative to be adsorbed on the surface of thesilica gel.

Further, then, 3 g of the N-acryloylaminopropyl silica gel wherein the4-vinylbenzoylated cellulose was adsorbed thereto was dispersed in 50 mlof n-heptane, followed by the addition of 30 mg of benzoyl peroxide. Theobtained mixture was stirred at 80° C. for 4 hours to copolymerize theacryloyl groups (vinyl groups) introduced into the silica gel with the4-vinylbenzoylated cellulose, thus giving a polymeric optical resolutionagent wherein the cellulose derivative was chemically bonded to thesurface of the silica gel.

The polymeric optical resolution agent thus prepared was used as apacking which was packed in a column of a high-performance liquidchromatography apparatus to determine the influences of the injection ofmethylene chloride on the number of theoretical plates and the retentionas compared with the case that an optical resolution agent comprising asilica gel wherein 4-vinylbenzoylated cellulose was only adsorbed on thesurface of the silica gel was used as an adsorption-type packing. Thatis, both the adsorption-type and polymeric cellulose derivative packingswere examined for the influences of the injection of methylene chlorideon the number of theoretical plates with respect to benzene and theretention time of stilbene oxide. The results are given in FIGS. 1 and2.

As shown in FIGS. 1 and 2, the number of theoretical plates of theadsorption-type packing lowered to 3000 from the initial value of about8300 by the injection of 20 μl of methylene chloride, and to below 1000by the injection of 200 μl thereof, which can be presumed that thenumber of theoretical plates was lowered because the methylene chlorideinjected might dissolve part of the cellulose derivative to disturb thestationary phase. Further, the retention time was not affected by theinjection of about 20 to 50 μl of methylene chloride, therefore it wasthought that the elution of the cellulose derivative was not occured.When 100 μl or above of methylene chloride was injected at once,however, the retention rapidly lowered and the elution of the cellulosederivative was observed. From these results, it can be understood thatmethylene chloride cannot be used as a solvent for dissolving a samplewhen the adsorption-type packing is used and it can be presumed thatsuch a lowering in the retention will occur similarly when a solventhaving a solubility parameter of about 18 to 25 is injected.

On the other hand, when the polymeric, chemically bonded packing of thepresent invention was used, no difference was observed in retentiontime, the number of theoretical plates or optical resolving power beforeand after the injection of methylene chloride, which clearly showed thatthe packing of the present invention is extremely excellent in theinsolubility in organic solvents.

Further, the optical resolving powers exhibited were examined in thecase of using a mobile phase containing tetrahydrofuran, which is a goodsolvent for the cellulose derivative, as an additive. As a result, asshown in FIGS. 3(a) and (b), it was ascertained that the polymericpacking according to the present invention exhibited an opticalresolving power even when a mobile phase containing 30% oftetrahydrofuran (THF) was used and that the optical resolving power wasmaintained even when 50% of tetrahydrofuran was contained in the mobilephase. The gas chromatography was conducted under the followingconditions:

column: polymeric vinylbenzoylcellulose

column sizes: 4.6 mm (inner diameter)×150 mm (length)

mobile phase:

(a) hexane/THF (7:3)

(b) hexane/THF (5:5)

flow rate: 1.0 ml/min

detection: UV (254 nm)

sample: warfarin.

On the other hand, in the case of using the adsorption-type packingwherein 4-vinylbenzoylated cellulose was only adsorbed, the elution ofthe stationary phase was observed when only 30% of tetrahydrofuran wasadded, and the chromatographic analysis was impossible because of alowered retention and a disturbed base line.

As described above, the optical resolution agent according to thepresent invention prepared by polymerizing a polysaccharide derivativeon the surface of a porous support exhibits an optical resolving powerequivalent to that of the adsorption-type optical resolution agent ofthe prior art prepared by causing a polysaccharide derivative to beadsorbed on the surface of a porous support. Further, the polysaccharidederivative is not eluted even with an organic solvent which could not beused for the adsorption-type optical resolution agents when the opticalresolution agent according to the present invention is employed. Thus,the optical resolution agent according to the present invention isextremely useful as a polysaccharide derivative type one which permitsthe use of various organic solvents.

We claim:
 1. An optical resolution agent prepared by polymerizing apolysaccharide derivative having vinyl groups introduced into thehydroxyl groups thereof through an ester or urethane linkage on thesurface of a porous support.
 2. An optical resolution agent prepared bycopolymerizing a polysaccharide derivative having vinyl groupsintroduced into the hydroxyl groups thereof through an ester or urethanelinkage with a porous support having vinyl groups introduced thereinto.3. A process for the preparation of an optical resolution agent,characterized by causing a polysaccharide derivative having vinyl groupsintroduced into the hydroxyl groups thereof through an ester or urethanelinkage to be adhered or adsorbed on the surface of a porous support andpolymerizing the polysaccharide derivative.
 4. A process for thepreparation of an optical resolution agent, characterized by causing apolysaccharide derivative having vinyl groups introduced into thehydroxyl groups thereof through an ester or urethane linkage to beadhered or adsorbed on the surface of a porous support having vinylgroups introduced thereinto and polymerizing the polysaccharidederivative with at least part of the polysaccharide derivative beingcopolymerized with the vinyl groups of the porous support.
 5. A processfor the optical resolution of a racemic modification with the opticalresolution agent as set forth in claim
 1. 6. A process for the opticalresolution of a racemic modification with the optical resolution agentas set forth in claim 2.